When a fear conditioned organism is exposed repeatedly to a fear-eliciting cue in the absence of any aversive event, the conditioned fear response declines and ultimately disappears. This process is known as fear extinction. In most cases extinction is believed to represent inhibition of fear, but extinction may involve erasure of fear if extinction training occurs very shortly after fear acquisition. Therefore, comparison of short (10 min) and long (72 hr) interval extinction may be used to elucidate the neurobiological mechanisms of fear inhibition vs. fear erasure. Preliminary data suggest differential involvement of NMDA receptors: expression of p44/42 MAPK and the NR2B (but not NR1) subunit of the NMDA receptor decreases within the amygdala following 10 min extinction, and 10 min extinction is not affected by administration of an NMDA receptor antagonist whereas 72 hr extinction is blocked. Understanding this issue will be important in terms of advancing understanding of the neurobiology of learning and memory, as well as from a clinical perspective. This proposal aims to employ a combination of biochemical and pharmacologic techniques to dissect the mechanisms of extinction as inhibition vs. erasure of fear. [unreadable] [unreadable] [unreadable]